How to use power Doppler ultrasound in transvaginal assessment of uterine fibroids.

Measuring vascularization in uterine fibroids is important for their diagnosis, treatment and prognosis. Vascularization can be measured by power Doppler ultrasound. The power Doppler signal depends on fibroid characteristics and on a variety of ultrasound-machine settings. Literature describing which machine settings influence the power Doppler signal is limited. Each manufacturer names settings and presets at their own discretion, with little information available publicly. Consistency of machine settings is important for correct interpretation of images in daily practice and is essential in yielding reproducible data for research. The aims of this paper, drawing from both a literature search and semistructured interviews with ultrasound-machine engineers and clinical experts in gynecological ultrasound, were: (1) to provide comprehensive background information on ultrasound physics and fibroid characteristics; (2) to present an overview of machine settings relevant to both two- and three-dimensional power Doppler, including power Doppler frequency, pulse repetition frequency, gain, wall-motion filter, acoustic power, persistence and signal rise; and (3) to provide a step-by-step tutorial on the optimal settings for vascular evaluation of uterine fibroids using power Doppler. The step-by-step tutorial comprises six steps to optimize the power Doppler signal, create a preset and acquire a reliable three-dimensional volume. This step-by-step tutorial should help research groups and clinicians to use power Doppler correctly and reproducibly in the evaluation of uterine fibroids. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Consensus on revised definitions of Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis: results of modified Delphi procedure.

OBJECTIVES: To evaluate whether the Morphological Uterus Sonographic Assessment (MUSA) features of adenomyosis need to be better defined and, if deemed necessary, to reach consensus on the updated definitions. METHODS: A modified Delphi procedure was performed among European gynecologists with expertise in ultrasound diagnosis of adenomyosis. To identify MUSA features that might need revision, 15 two-dimensional (2D) video recordings (four recordings also included three-dimensional (3D) still images) of transvaginal ultrasound (TVS) examinations of the uterus were presented in the first Delphi round (online questionnaire). Experts were asked to confirm or refute the presence of each of the nine MUSA features of adenomyosis (described in the original MUSA consensus statement) in each of the 15 videoclips and to provide comments. In the second Delphi round (online questionnaire), the results of the first round and suggestions for revision of MUSA features were shared with the experts before they were asked to assess a new set of 2D and 3D still images of TVS examinations and to provide feedback on the proposed revisions. A third Delphi round (virtual group meeting) was conducted to discuss and reach final consensus on revised definitions of MUSA features. Consensus was predefined as at least 66.7% agreement between experts. RESULTS: Of 18 invited experts, 16 agreed to participate in the Delphi procedure. Eleven experts completed and four experts partly finished the first round. The experts identified a need for more detailed definitions of some MUSA features. They recommended use of 3D ultrasound to optimize visualization of the junctional zone. Fifteen experts participated in the second round and reached consensus on the presence or absence of ultrasound features of adenomyosis in most of the still images. Consensus was reached for all revised definitions except those for subendometrial lines and buds and interrupted junctional zone. Thirteen experts joined the online meeting, in which they discussed and agreed on final revisions of the MUSA definitions. There was consensus on the need to distinguish between direct features of adenomyosis, i.e. features indicating presence of ectopic endometrial tissue in the myometrium, and indirect features, i.e. features reflecting changes in the myometrium secondary to presence of endometrial tissue in the myometrium. Myometrial cysts, hyperechogenic islands and echogenic subendometrial lines and buds were classified unanimously as direct features of adenomyosis. Globular uterus, asymmetrical myometrial thickening, fan-shaped shadowing, translesional vascularity, irregular junctional zone and interrupted junctional zone were classified as indirect features of adenomyosis. CONCLUSION: Consensus between gynecologists with expertise in ultrasound diagnosis of adenomyosis was achieved regarding revised definitions of the MUSA features of adenomyosis and on the classification of MUSA features as direct or indirect signs of adenomyosis. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Assessment of protein biomarkers for preoperative differential diagnosis between benign and malignant ovarian tumors.

OBJECTIVE: To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors. METHODS: In this exploratory diagnostic study, 254 patients with an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospitals Leuven (128 benign, 42 borderline, 22 stage I, 55 stage II-IV, and 7 secondary metastatic tumors). The quantification of 33 serum proteins was done preoperatively, using multiplex high throughput immunoassays (Luminex) and electrochemiluminescence immuno-assay (ECLIA). We calculated univariable areas under the Receiver Operating Characteristic Curves (AUCs). To discriminate malignant from benign tumors, multivariable ridge logistic regression with backward elimination was performed, using bootstrapping to validate the resulting AUCs. RESULTS: CA125 had the highest univariable AUC to discriminate malignant from benign tumors (0.85, 95% confidence interval 0.79-0.89). Combining CA125 with CA72.4 and HE4 increased the AUC to 0.87. For benign vs borderline tumors, CA125 had the highest univariable AUC (0.74). For borderline vs stage I malignancy, no proteins were promising. For stage I vs II-IV malignancy, CA125, HE4, CA72.4, CA15.3 and LAP had univariable AUCs ≥0.80. CONCLUSIONS: The results confirm the dominant role of CA125 for identifying malignancy, and suggest that other markers (HE4, CA72.4, CA15.3 and LAP) may help to distinguish between stage I and stage II-IV malignancies. However, further research is needed, also to investigate the added value over clinical and ultrasound predictors of malignancy, focusing on the differentiation between subtypes of malignancy.

IDEAL study: magnetic resonance imaging for suspected deep endometriosis assessment prior to laparoscopy is as reliable as radiological imaging as a complement to transvaginal ultrasonography.

OBJECTIVE: To compare the value of using one-stop magnetic resonance imaging (MRI) vs standard radiological imaging as a supplement to transvaginal ultrasonography (TVS) for the preoperative assessment of patients with endometriosis referred for surgery in a tertiary care academic center. METHODS: This prospective observational study compared the diagnostic value of the standard preoperative imaging practice of our center, which involves expert TVS complemented by intravenous urography (IVU) for the evaluation of the ureters and double-contrast barium enema (DCBE) for the evaluation of the rectum, sigmoid and cecum, with that of expert TVS complemented by a 'one-stop' MRI examination evaluating the upper abdomen, pelvis, kidneys and ureters as well as rectum and sigmoid on the same day, for the preoperative triaging of 74 women with clinically suspected deep endometriosis. The findings at laparoscopy were considered the reference standard. Patients were stratified according to their need for monodisciplinary surgical approach, carried out by gynecologists only, or multidisciplinary surgical approach, involving abdominal surgeons and/or urologists, based on the extent to which endometriosis affected the reproductive organs, bowel, ureters, bladder or other abdominal organs. RESULTS: Our standard preoperative imaging approach and the combined findings of TVS and MRI had similar diagnostic performance, resulting in correct stratification for a monodisciplinary or a multidisciplinary surgical approach of 67/74 (90.5%) patients. However, there were differences between the estimation of the severity of disease by DCBE and MRI. The severity of rectal involvement was underestimated in 2.7% of the patients by both TVS and DCBE, whereas it was overestimated in 6.8% of the patients by TVS and/or DCBE. CONCLUSIONS: Complementary to expert TVS, 'one-stop' MRI can predict intraoperative findings equally well as standard radiological imaging (IVU and DCBE) in patients referred for endometriosis surgery in a tertiary care academic center. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Can risk factors, clinical history and symptoms be used to predict risk of ectopic pregnancy in women attending an early pregnancy assessment unit?

OBJECTIVE: To examine whether risk factors and symptoms may be used to predict the likelihood of ectopic pregnancy (EP) in women attending early pregnancy assessment units in the UK. METHODS: This was an observational cohort study of pregnant women under 12 weeks' gestation who were recruited from three London university hospitals between August 2012 and April 2013. One hospital continued recruitment between January and June 2015. A standardized information sheet incorporating patient demographics, medical history and symptoms was completed by patients and confirmed by examining clinicians. The outcome measure was final pregnancy location. RESULTS: There were 1320 eligible patients included in the analysis, with a total of 72 EPs (rate of 6%). Pelvic pain and diarrhea > three times in the previous 24 h were independent symptoms that increased the risk of EP, with relative risks of 2.4 (95% CI, 1.4-4.0; P = 0.002) and 2.2 (95% CI, 1.08-4.5; P = 0.03), respectively. The only other independent marker of risk of EP was duration of vaginal bleeding; the risk of EP increased by 20% (95% CI, 14%-27%) for every 1-day increment in duration (P < 0.001). A logistic regression model incorporating these factors demonstrated an area under the receiver-operating characteristics curve of 0.73 (95% CI, 0.67-0.79). The prevalence of EP was low when there was no pelvic pain, no diarrhea and the duration of bleeding was ≤ 3 days, with an EP rate of 2% (6/391). In the presence of a single risk factor, the EP rate increased to 5% (29/631) when only pelvic pain was present, 8% (1/12) when only diarrhea > three times in the previous 24 h was reported and 9% (9/103) when there was only vaginal bleeding with a duration > 3 days. Women with pelvic pain and vaginal bleeding of any severity for > 3 days had a high EP rate of 16% (23/146). In the nine women who also reported diarrhea > three times in the previous 24 h, two had EP. CONCLUSIONS: Only the presence of pelvic pain, diarrhea > three times in the previous 24 h and duration of bleeding were symptoms that significantly increased the risk for EP in women attending early pregnancy assessment units. Risk factors and symptoms alone could not be used to predict reliably an EP. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Subjective assessment versus ultrasound models to diagnose ovarian cancer: A systematic review and meta-analysis.

INTRODUCTION: Many national guidelines concerning the management of ovarian cancer currently advocate the risk of malignancy index (RMI) to characterise ovarian pathology. However, other methods, such as subjective assessment, International Ovarian Tumour Analysis (IOTA) simple ultrasound-based rules (simple rules) and IOTA logistic regression model 2 (LR2) seem to be superior to the RMI. Our objective was to compare the diagnostic accuracy of subjective assessment, simple rules, LR2 and RMI for differentiating benign from malignant adnexal masses prior to surgery. MATERIALS AND METHODS: MEDLINE, EMBASE and CENTRAL were searched (January 1990-August 2015). Eligibility criteria were prospective diagnostic studies designed to preoperatively predict ovarian cancer in women with an adnexal mass. RESULTS: We analysed 47 articles, enrolling 19,674 adnexal tumours; 13,953 (70.9%) benign and 5721 (29.1%) malignant. Subjective assessment by experts performed best with a pooled sensitivity of 0.93 (95% confidence interval [CI] 0.92-0.95) and specificity of 0.89 (95% CI 0.86-0.92). Simple rules (classifying inconclusives as malignant) (sensitivity 0.93 [95% CI 0.91-0.95] and specificity 0.80 [95% CI 0.77-0.82]) and LR2 (sensitivity 0.93 [95% CI 0.89-0.95] and specificity 0.84 [95% CI 0.78-0.89]) outperformed RMI (sensitivity 0.75 [95% CI 0.72-0.79], specificity 0.92 [95% CI 0.88-0.94]). A two-step strategy using simple rules, when inconclusive added by subjective assessment, matched test performance of subjective assessment by expert examiners (sensitivity 0.91 [95% CI 0.89-0.93] and specificity 0.91 [95% CI 0.87-0.94]). CONCLUSIONS: A two-step strategy of simple rules with subjective assessment for inconclusive tumours yielded best results and matched test performance of expert ultrasound examiners. The LR2 model can be used as an alternative if an expert is not available.

Subjective ultrasound assessment, the ADNEX model and ultrasound-guided tru-cut biopsy to differentiate disseminated primary ovarian cancer from metastatic non-ovarian cancer.

OBJECTIVES: To compare subjective ultrasound assessment and the ADNEX model with ultrasound-guided tru-cut biopsy to differentiate disseminated primary ovarian cancer from metastatic non-ovarian cancer. METHODS: This was a prospective study including 143 consecutive women with disseminated malignancy of unknown primary origin, with a pelvic tumor/carcinosis. Women underwent either transvaginal or transrectal ultrasound as well as transabdominal ultrasound examination followed by tru-cut biopsy. The ultrasound examiner assessed tumor morphology, spread in the pelvis and abdomen, and predicted tumor origin as primary ovarian or metastatic using both subjective assessment and the ADNEX model. Histology from tru-cut biopsy served as the gold standard for assessment of diagnostic accuracy. Biopsy adequacy and the complication rate were assessed. RESULTS: Tru-cut biopsy was performed transvaginally in 131/143 (92%) women. Two women needed inpatient care (one had abdominal wall hematoma, and one infection). Biopsy resulted in a conclusive diagnosis in 126/143 (88%) women, amongst whom cytoreductive surgery was performed in 30/126 confirming the diagnosis in all cases. Non-ovarian metastatic cancer was found in 37/126 (29%) women and primary ovarian cancer in 89/126 (71%) women. Subjective ultrasound evaluation had a sensitivity of 82% (73/89) and a specificity of 70% (26/37) in predicting primary ovarian cancer. The ADNEX model had an area under the receiver-operating characteristics curve of 0.891 (95% CI, 0.794-0.946) (in women with an ovarian lesion, n = 104). Tumor origin was associated with age, CA 125, previous neoplasia, presence of omental cake and tumor mobility. CONCLUSIONS: Subjective ultrasound assessment and the ADNEX model can both be used to predict whether a pelvic tumor is metastatic and of non-ovarian origin, indicating the need for tru-cut biopsy, which is associated with very few complications and will provide a conclusive diagnosis in nine out of 10 women. Copyright © 2015 ISUOG.

Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group.

The MUSA (Morphological Uterus Sonographic Assessment) statement is a consensus statement on terms, definitions and measurements that may be used to describe and report the sonographic features of the myometrium using gray-scale sonography, color/power Doppler and three-dimensional ultrasound imaging. The terms and definitions described may form the basis for prospective studies to predict the risk of different myometrial pathologies, based on their ultrasound appearance, and thus should be relevant for the clinician in daily practice and for clinical research. The sonographic features and use of terminology for describing the two most common myometrial lesions (fibroids and adenomyosis) and uterine smooth muscle tumors are presented.

Evaluating myometrial and cervical invasion in women with endometrial cancer: comparing subjective assessment with objective measurement techniques.

OBJECTIVE: To compare the diagnostic accuracy of subjective ultrasound assessment with that of objective measurement techniques in the evaluation of myometrial and cervical invasion in women with endometrial cancer. METHODS: This was a prospective multicenter study including 144 women with endometrial cancer undergoing transvaginal ultrasound. Myometrial and cervical invasion was evaluated subjectively, as well as objectively measured in different ways: endometrial thickness, tumor/uterine anteroposterior (AP) diameter ratio, minimal tumor-free margin, minimal tumor-free margin/uterine AP diameter ratio, tumor volume (three-dimensional (3D)), tumor/uterine volume (3D) ratio, and distance from outer cervical os to lower margin of tumor (Dist-OCO). Histological assessment following hysterectomy was the gold standard. RESULTS: The sensitivity (72%) and specificity (76%) of tumor/uterine AP diameter (at cut-off, 0.53) were not significantly different from those of subjective evaluation (sensitivity, 77% (P = 0.44); specificity, 81% (P = 0.32)) for the prediction of deep myometrial invasion; all other objective measurement techniques had either a significantly lower sensitivity or a lower specificity. For all objective measurement techniques, except minimal tumor-free margin/uterine AP diameter ratio, fixing the sensitivity at the same level as that of subjective evaluation (i.e. 77%) gave a significantly lower specificity. Dist-OCO was the only parameter that might have potential to predict cervical invasion; it had a non-significantly higher sensitivity than did subjective evaluation (73% vs 54%, P = 0.06), but a significantly lower specificity (63% vs 93%, P < 0.001). CONCLUSION: Subjective assessment of cervical and myometrial invasion is as good as or better than any objective measurement technique. The tumor/uterine AP diameter ratio and minimal tumor-free margin/uterine AP diameter ratio seem to be the best objective measurement techniques to predict deep myometrial invasion. It remains to be shown if objective measurements are useful to predict cervical invasion.

Multicentre external validation of IOTA prediction models and RMI by operators with varied training.

BACKGROUND: Correct characterisation of ovarian tumours is critical to optimise patient care. The purpose of this study is to evaluate the diagnostic performance of the International Ovarian Tumour Analysis (IOTA) logistic regression model (LR2), ultrasound Simple Rules (SR), the Risk of Malignancy Index (RMI) and subjective assessment (SA) for preoperative characterisation of adnexal masses, when ultrasonography is performed by examiners with different background training and experience. METHODS: A 2-year prospective multicentre cross-sectional study. Thirty-five level II ultrasound examiners contributed in three UK hospitals. Transvaginal ultrasonography was performed using a standardised approach. The final outcome was the surgical findings and histological diagnosis. To characterise the adnexal masses, the six-variable prediction model (LR2) with a cutoff of 0.1, the RMI with cutoff of 200, ten SR (five rules for malignancy and five rules for benignity) and SA were applied. The area under the curves (AUCs) for performance of LR2 and RMI were calculated. Diagnostic performance measures for all models assessed were sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and the diagnostic odds ratio (DOR). RESULTS: Nine-hundred and sixty-two women with adnexal masses underwent transvaginal ultrasonography, whereas 255 had surgery. Prevalence of malignancy was 29% (49 primary invasive epithelial ovarian cancers, 18 borderline ovarian tumours, and 7 metastatic tumours). The AUCs for LR2 and RMI for all masses were 0.94 (95% confidence interval (CI): 0.89-0.97) and 0.90 (95% CI: 0.83-0.94), respectively. In premenopausal women, LR2-RMI difference was 0.09 (95% CI: 0.03-0.15) compared with -0.02 (95% CI: -0.08 to 0.04) in postmenopausal women. For all masses, the DORs for LR2, RMI, SR+SA (using SA when SR inapplicable), SR+MA (assuming malignancy when SR inapplicable), and SA were 62 (95% CI: 27-142), 43 (95% CI: 19-97), 109 (95% CI: 44-274), 66 (95% CI: 27-158), and 70 (95% CI: 30-163), respectively. CONCLUSION: Overall, the test performance of IOTA prediction models and rules as well as the RMI was maintained in examiners with varying levels of training and experience.

Does the presence of a Caesarean section scar affect implantation site and early pregnancy outcome in women attending an early pregnancy assessment unit?

STUDY QUESTION: Are there any differences in the location and distance to the internal cervical ostium of the implantation site of the intrauterine gestation sacs, early pregnancy symptoms and pregnancy outcome at 12 weeks gestation between women with and without a previous Caesarean section (CS)? SUMMARY ANSWER: The presence of a CS scar affects the site of implantation, and the distance between implantation site and the scar is related to the risk of spontaneous abortion. WHAT IS KNOWN ALREADY?: Little is known about the impact of a CS scar on implantation other than the risk of Caesarean scar pregnancy (CSP). Furthermore, there is a paucity of information on how the proximity of implantation to the scar impacts on pregnancy outcome in the first trimester. STUDY DESIGN, SIZE, AND DURATION: A prospective cohort study conducted over 15 months in the early pregnancy unit of a London Teaching Hospital. Three hundred and eighty women underwent a transvaginal scan at 6-11 weeks of gestation. A total of 170 women had undergone ≥1 CS, and 210 women had no history of CS. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 380 women were recruited as consecutive non-selected cases. The relationship between the implanted sac and the CS scar was assessed by quantifiable measures and by subjective impression. Logistic regression analysis was used to determine the influence of the presence of a CS scar on pregnancy outcome. The final outcome of the study was the viability of the pregnancy at 12 weeks. MAIN RESULTS AND THE ROLE OF CHANCE: Implantation was most frequently posterior (53%) in the CS group and fundal in the non-CS group (42%). Gestation sac implantation was 8.7 mm lower in the CS group (95% confidence interval (CI) 6.7-10.7, P < 0.0001). Presenting complaints differed in women with and without a previous CS (P = 0.0009). More frequent vaginal bleeding [73 versus 55%, difference -18, 95% CI (-27 to -8%] yet no clearly increased spontaneous abortion rates were noted in the CS group compared with the non-CS group (adjusted odds ratio = 1.1, 95% CI 0.6-1.9, P = 0.74). Subjective impression showed that in eight cases the implantation site crossed the scar, seven of which resulted in spontaneous abortion, while the remaining case survived to term complicated by placenta praevia and post-partum haemorrhage. The subjective impression of the examiner was supported by the measurements of distance between implantation site and CS scar. LIMITATIONS, REASONS FOR CAUTION: A weakness of the study is the lack of a reference technique to verify the location of implantation. WIDER IMPLICATIONS OF THE FINDINGS: This study adds further support to the hypothesis that the presence of a CS on the uterus impacts on the implantation site of a future pregnancy. The possibility that the CS scar has an impact on the risk of spontaneous abortion should be further studied. Caution must be exercised when implantation occurs near to, and crosses, a CS scar as this is not always associated with the diagnosis of CSP. A potential limitation of the study is that we did not examine scar dimensions and morphology.

Clinically oriented three-step strategy for assessment of adnexal pathology.

OBJECTIVE: To determine the diagnostic performance of ultrasound-based simple rules, risk of malignancy index (RMI), two logistic regression models (LR1 and LR2) and real-time subjective assessment by experienced ultrasound examiners following the exclusion of masses likely to be judged as easy and 'instant' to diagnose by an ultrasound examiner, and to develop a new strategy for the assessment of adnexal pathology based on this. METHODS: 3511 patients with at least one persistent adnexal mass preoperatively underwent transvaginal ultrasonography to assess tumor morphology and vascularity. They were included in two consecutive prospective studies by the International Ovarian Tumor Analysis (IOTA) group: Phase 1 (1999-2005), development of the simple rules and logistic regression models LR1 and LR2, and Phase 2, a validation study (2005-2007). RESULTS: Almost half of the cases (43%) were identified as 'instant' to diagnose on the basis of descriptors applied to the database. To assess diagnostic performance in the more difficult 'non-instant' masses, we used only Phase 2 data (n = 1036). The sensitivity of LR2 was 88%, of RMI it was 41% and of subjective assessment it was 87%. The specificity of LR2 was 67%, of RMI it was 90% and of subjective assessment it was 86%. The simple rules yielded a conclusive result in almost 2/3 of the masses, where they resulted in sensitivity and specificity similar to those of real-time subjective assessment by experienced ultrasound examiners: sensitivity 89 vs 89% (P = 0.76), specificity 91 vs 91% (P = 0.65). When a three-step strategy was applied with easy 'instant' diagnoses as Step 1, simple rules where conclusive as Step 2 and subjective assessment by an experienced ultrasound examiner in the remaining masses as Step 3, we obtained a sensitivity of 92% and specificity of 92% compared with sensitivity 90% (P = 0.03) and specificity 93% (P = 0.44) when using real-time subjective assessment by experts in all tumors. CONCLUSION: A diagnostic strategy using simple descriptors and ultrasound rules when applied to the variables contained in the IOTA database obtains results that are at least as good as those obtained by subjective assessment of a mass by an expert.

Pre-sampling ultrasound evaluation and assessment of the tissue yield during sampling improves the diagnostic reliability of office endometrial biopsy.

We evaluated the implementation of a strict procedure for endometrium biopsy, including pre-sampling ultrasound examination and assessment of the tissue yield during sampling, in 257 consecutive women with abnormal bleeding. The tissue yield was assessed during sampling and scored from 1 to 4. The median endometrial thickness as measured by ultrasound was 5.0 mm, 5.1 mm, 10.0 mm and 18.7 mm for a tissue yield score of 1, 2, 3 and 4, respectively. The median endometrial thickness at ultrasound and the median tissue yield score was 18.3 mm and score 4 in the endometrial cancer cases, compared with 3.9 mm and score 1, and 14.8 mm and score 3 in the case of endometrial atrophy and hyperplasia, respectively; and 11.5 mm and score 2 in endometrial polyp cases. Overall, 12 cancers were diagnosed. No endometrial cancer was diagnosed during follow-up (median 447 days). A strict office endometrial biopsy procedure contributes to the diagnostic reliability for intracavitary pathology.

Ultrasound assessment of the peri-implantation uterus: a review.

Emerging evidence suggests that early embryo implantation is a more active maternal process than hitherto appreciated, involving active encapsulation of the implanting blastocyst by maternal decidual cells and coordinated changes in the underlying inner myometrium, known as the junctional zone. These concepts raise the possibility that early ultrasound markers predictive of adverse pregnancy outcome could be identified. In this review we assess the role of ultrasound in predicting the likelihood of different pregnancy outcomes and highlight potential novel markers that could be tested.

Adnexal masses difficult to classify as benign or malignant using subjective assessment of gray-scale and Doppler ultrasound findings: logistic regression models do not help.

OBJECTIVE: To develop a logistic regression model that can discriminate between benign and malignant adnexal masses perceived to be difficult to classify by subjective evaluation of gray-scale and Doppler ultrasound findings (subjective assessment) and to compare its diagnostic performance with that of subjective assessment, serum CA 125 and the risk of malignancy index (RMI). METHODS: We used data from the 3511 patients with an adnexal mass included in the International Ovarian Tumor Analysis (IOTA) studies. All patients had been examined using transvaginal gray-scale and Doppler ultrasound following a standardized research protocol carried out by an experienced ultrasound examiner using a high-end ultrasound system. In addition to prospectively collecting information on > 40 clinical and ultrasound variables, the ultrasound examiner classified each mass as certainly or probably benign, unclassifiable, or certainly or probably malignant. A logistic regression model to discriminate between benignity and malignancy was developed for the unclassifiable masses (n = 244, i.e. 7% of all tumors) using a training set (160 tumors, 45 malignancies) and then tested on a test set (84 tumors, 28 malignancies). The gold standard was the histological diagnosis of the surgically removed adnexal mass. The area under the receiver-operating characteristics curve (AUC), sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were used to describe diagnostic performance and were compared between subjective assessment, CA 125, the RMI and the logistic regression model created. RESULTS: One variable was retained in the logistic regression model: the largest diameter (in mm) of the largest solid component of the tumor (odds ratio (OR) = 1.04; 95% CI, 1.02-1.06). The model had an AUC of 0.68 (95% CI, 0.59-0.78) on the training set and an AUC of 0.65 (95% CI, 0.53-0.78) on the test set. On the test set, a cut-off of 25% probability of malignancy (corresponding to the largest diameter of the largest solid component of 23 mm) resulted in a sensitivity of 64% (18/28), a specificity of 55% (31/56), an LR+ of 1.44 and an LR- of 0.65. The corresponding values for subjective assessment were 68% (19/28), 59% (33/56), 1.65 and 0.55. On the test set of patients with available CA 125 results, the LR+ and LR- of the logistic regression model (cut-off = 25% probability of malignancy) were 1.29 and 0.73, of subjective assessment were 1.45 and 0.63, of CA 125 (cut-off = 35 U/mL) were 1.24 and 0.84 and of RMI (cut-off = 200) were 1.21 and 0.92. CONCLUSIONS: About 7% of adnexal masses that are considered appropriate for surgical removal cannot be classified as benign or malignant by experienced ultrasound examiners using subjective assessment. Logistic regression models to estimate the risk of malignancy, CA 125 measurements and the RMI are not helpful in these masses.

Effect of cancer prevalence on the use of risk-assessment cut-off levels and the performance of mathematical models to distinguish malignant from benign adnexal masses.

OBJECTIVE: Two logistic regression models have been developed for the characterization of adnexal masses. The goal of this prospective analysis was to see whether these models perform differently according to the prevalence of malignancy and whether the cut-off levels of risk assessment for malignancy by the models require modification in different centers. METHODS: Centers were categorized into those with a prevalence of malignancy below 15%, between 15 and 30% and above 30%. The areas under the receiver-operating characteristics curves (AUC) were compared using bootstrapping. The optimal cut-off level of risk assessment for malignancy was chosen per center, corresponding to the highest sensitivity level possible while still keeping a good specificity. RESULTS: Both models performed better in centers with a lower prevalence of malignant cases. The AUCs of the two models for centers with fewer than 15% malignant cases were 0.97 and 0.95, those of centers with 15-30% malignancy were 0.95 and 0.93 and those of centers with more than 30% malignant cases were 0.94 and 0.92. This decrease in performance was due mainly to the decrease in specificity from over 90 to around 76%. In the centers with a higher percentage of malignant cases, a sensitivity of at least 90% with a good specificity could not be obtained by choosing a different cut-off level. CONCLUSIONS: Overall the models performed well in all centers. The performance of the logistic regression models worsened with increasing prevalence of malignancy, due to a case mix with more borderline and complex benign masses seen in those centers. Because the cut-off of 0.10 is optimal for all three types of center, it seems reasonable to use this cut-off for both models in all centers.

Functional linear discriminant analysis: a new longitudinal approach to the assessment of embryonic growth.

BACKGROUND: Functional linear discriminant analysis (FLDA) is a new growth assessment technique using serial measurements to discriminate between normal and abnormal fetal growth. We used FLDA to assess and compare growth in live pregnancies destined to miscarry with those remaining viable. METHODS: This was a prospective cohort study of women with ultrasound scans on at least two separate occasions showing live pregnancies. Serial crown-rump length (CRL), mean gestational sac diameter and mean yolk sac diameter measurements were recorded. The ability of FLDA to predict subsequent miscarriage was compared with that of a single CRL measurement. RESULTS: Of 521 included pregnancies, 493 (94.6%) remained viable at 14 weeks and 28 (5.4%) miscarried. The CRL growth rate was significantly lower in those that miscarried (one-sample t-test, P = 2.638E-22). The sensitivity of FLDA in predicting miscarriage from serial CRL measurements was 60.7% and specificity was 93.1% [positive predictive value (PPV) 33.3%, negative predictive value (NPV) 97.7%]. This was significantly better for predicting miscarriage than a single CRL observation of more than 2SD below that expected (sensitivity 53.6%, specificity 72.2%, PPV 9.9%, NPV 96.5%). CONCLUSIONS: FLDA discriminates between normal and abnormal growth to predict miscarriage with high specificity. FLDA predicts miscarriage better than a single observation of a small CRL.